OBJECTIVES: 1. "The Neuron-Target Interactions Which Control Axonal Sprouting in Vivo and in Vitro". We will extend our present correlative electrophysiological and ultrastructural studies on nerve sprouting "in vivo", using the skin of lower vertebrates. These studies suggest: (a) that Merkel cells of the epidermis develop independently of nerves; (b) that they evoke directional sprouting of mechanosensory nerves towards them, so controlling the branching and density of the endings: (c) that this trophic role disappears after Merkel cell innervation; (d) that it reappears if a presumed restraining nerve influence is removed by nerve section or by reduction of axoplasmic transport. In addition, co-cultures of dorsal root ganglion cells and epidermis will be studied "in vitro" to investigate the neuron-target cell interactions and the nature of the sprouting stimulus, under controlled conditions. 2. "The regulation of the Areas of Nerve Fields and the Concept of Domains". Our suggestion of "domains" - preferred territories for occupancy by intact nerves - will be further tested in salamanders, Xenopus and rats, utilizing both collateral sprouting evoked by adjacent denervation, and regeneration after nerve section. The experiments, in which mechanosensory nerve fileds of skin are mapped electrophysiologically, include re-direction of and competition among nerves, and skin transplantations, in both adults and neonates. 3. "The Peripheral Nerve-Field Influence on Development of Cutaneous Reflexes in the Mammal in the Rat" sensory stimulation of the back skin causes a reflex contraction of the underlying extensive cutaneous striated muscle. Our pilot studies show: (a) that this contraction is localized to the site of sensory stimulation and to the corresponding contralateral site i.e., the reflex shows "local sign", and (b) that in neonatal rats (but not adults) when central circuitry is still developing, the field of a sensory nerve will enlarge by collateral sprouting after adjacent denervation. We will investigate how variations in peripheral nerve fields produced by: (1) collateral sprouting neonates, and (2) re-direction of cutaneous nerves, will affect the local sign of the reflex.